While many of you experience ‘March Madness’ as the NCAA basketball championship tournament, here at UPMC Hillman Cancer Center, it’s the preparation for and follow-up from the annual review by our External Advisory Board (EAB). Comprising a distinguished panel of scientists and physicians who are the directors and senior leaders of other National Cancer Institute (NCI)-designated Cancer Centers, our EAB visits once each year to review the quantity and quality of our science and the effectiveness and efficiency of our operations, in order to provide thoughtful recommendations on how we can further improve our research, training/education, and outreach missions. These reviews are in addition to the site visits conducted by NCI reviewers, once every five years.
At this year’s EAB meeting, we presented and discussed some of the strategic changes that we plan to introduce into our Cancer Center’s programmatic structure and leadership positions; the ways in which other organizations (including the large UPMC health care system, the University of Pittsburgh Clinical and Translational Science Institute, and county and state Departments of Health) are being leveraged for our research; and our success at advancing scientific discoveries into new directions of basic and translational research and into early-phase clinical trials, through multi-disciplinary collaboration.
As an example, Dr. Steffi Oesterreich, who is the Educational Director of the Women’s Cancer Research Center and is being proposed as leader of a re-configured Cancer Biology Program, has been actively studying the behavior of invasive lobular carcinoma (ILC) cells for several years. ILC is a subtype of breast cancer detected in up to 15% of all new breast cancer cases, affecting 26,000-34,000 women annually. Although ILC has historically been treated the same way as the much more common invasive ductal carcinoma (IDC) subtype, it does not show similar response. Patients with ILC whose pathology reports are positive for factors typically associated with a favorable prognosis, tend to not fare as well as those with IDC. Dr. Oesterreich’s laboratory has been characterizing how ILC cells in culture, animal models, and patient-derived tissue samples respond to stimulation by the female reproductive hormones estrogen and progesterone, and estrogen-blocking drugs such as tamoxifen. A key aspect of Dr. Oesterreich’s research is determining how ILC tumors with estrogen receptors become resistant to estrogen-blocking drugs. Of tremendous pride to all of us at Hillman, one postdoctoral fellow and two predoctoral trainees who are being mentored by Dr. Oesterreich—Dr. Nilgun Tasdemir, Ms. Emily Harrington, and Mr. Kevin Levine—were successful in competing for individual peer-reviewed funding awards from the Department of Defense Breast Cancer Research Program and the NCI to study different aspects of ILC biology. (Receiving individual grant awards while still in training is a strong predictor of future scientific career success.) Through collaboration with Hillman investigators that include Drs. Ben Van Houten, Adrian Lee, Dario Vignali, and George Tseng, Dr. Oesterreich has extended her lab’s studies of ILC into areas that include cellular metabolism, insulin-like growth factor signaling, interactions with the immune system, and alterations in levels of gene expression.
One of the highpoints of our EAB review this year was showing how Dr. Oesterreich’s bench-level science contributed to design and implementation of the first-ever clinical trial intended exclusively for patients with ILC. With funding from Susan G. Komen for the Cure, Dr. Rachel Jankowitz—a medical oncologist who specializes in treating breast cancer and directs the Magee-Womens Hospital of UPMC High Risk Breast Cancer Program—opened A Trial of Endocrine Response in Patients with Invasive Lobular Carcinoma (NCT02206984), which is actively accruing patients at Magee-Womens Hospital of UPMC and seven other Cancer Centers that belong to the Translational Breast Cancer Research Consortium. The randomized clinical trial is comparing three different hormonal therapy drugs that block the effects of estrogen via three different mechanisms of action, when administered prior to breast cancer surgery in 150 post-menopausal patients. To rapidly learn which of the three tested therapies is likely to have greatest clinical benefit, tumor tissue that is removed at the time of surgery will be analyzed for changes in a key marker of rapid cell growth (Ki67) and the levels and activity of estrogen receptor when compared to tumor obtained from the same patient during initial biopsy.
The work being conducted on ILC by Dr. Oesterreich and her Hillman collaborators has helped to increase national and international interest in ILC as a distinctly unique cancer type. In this regard, Dr. Oesterreich received an R13 conference grant from the NCI to chair the 1st International Invasive Lobular Breast Cancer Symposium, which was held in our own Herberman Conference Center in September 2016. The symposium brought together basic, translational, and clinical researchers, clinicians representing various oncology specialties, and ILC survivors, from around the globe, and led to formation of a new advocacy organization—the Lobular Breast Cancer Alliance—with its goals to advance ILC research, build organizational partnerships, and educate about ILC.
Of course, the “story” of how Hillman efforts are advancing the fight against ILC is only one of the many examples that we presented to our EAB. In the months to come, I intend to provide additional examples of how our researchers collaborate with each other, investigators from other institutions, and partner organizations. I also look forward to sharing the results of Dr. Jankowitz’s trial, following completion of patient recruitment and analysis.
Robert L. Ferris, MD, PhD